Kirstein, Frank, Horsnell, William G.C., Kuperman, Douglas A., Huang, Xiaozhu, Erle, David J., Lopata, Andreas L., and Brombacher, Frank (2010) Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma. The Journal of Allergy and Clinical Immunology, 126 (2). pp. 347-354.

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Abstract

Background

Airflow in the lungs of patients with allergic asthma is impaired by excessive mucus production and airway smooth muscle contractions. Elevated levels of the cytokines IL-4 and IL-13 are associated with this pathology. In vitro studies have suggested that IL-4 receptor α (IL-4Rα) signaling on smooth muscle cells is critical for airway inflammation and airway hyperresponsiveness. Objective

To define the contribution of IL-4 and IL-13 to the onset of asthmatic pathology, the role of their key receptor IL-4Rα in smooth muscle cells was examined in vivo. Methods

By using transgenic smooth muscle myosin heavy chaincreIL-4Rα-/lox mice deficient in IL-4Rα in smooth muscle cells, in vivo effects of impaired IL-4Rα signaling in smooth muscle cells on the outcome of asthmatic disease were investigated for the first time. Allergic asthma was introduced in mice by repeated sensitization with ovalbumin/aluminum hydroxide on days 0, 7, and 14, followed by intranasal allergen challenge on days 21 to 23. Mice were investigated for the presence of airway hyperresponsiveness, airway inflammation, allergen-specific antibody production, Th2-type cytokine responses, and lung pathology. Results

Airway hyperresponsiveness, airway inflammation, mucus production, Th2 cytokine production, and specific antibody responses were unaffected in smooth muscle myosin heavy chaincreIL-4Rα-/lox mice compared with control animals. Conclusion

The impairment of IL-4Rα on smooth muscle cells had no effect on major etiologic markers of allergic asthma. These findings suggest that IL-4Rα responsiveness in airway smooth muscle cells during the early phase of allergic asthma is not, as suggested, necessary for the outcome of the disease.

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